Study design and participants
We retrospectively recruited patients admitted with community-acquired pneumonia (CAP) hospitalized between August 2016 and December 2019 at six secondary and tertiary academic hospitals in China. The diagnosis of CAP was based on the American Thoracic Society and Infectious Disease Society of America (ATS/IDSA) guidelines . Immunocompromised patients were selected if they met any of the following inclusion criteria: (1) solid-organ, stem-cell, or bone-marrow transplant recipients; (2) undergoing chemotherapy for any hematological disease (including acute lymphocytic leukemia, acute myeloid leukemia, chronic lymphocytic leukemia, myeloma, or lymphoma) or presence of a solid tumor within 6 months of admission or neutropenia (neutrophil count < 500 cells/mm3); (3) chest radiation therapy within 3 months of admission; (4) autoimmune disease (including but not limited to systemic lupus erythematosus, rheumatoid arthritis, polymyalgia rheumatica, and interstitial lung disease) and receiving immunosuppressive therapy (including chronic glucocorticoid treatment: oral prednisone >10 mg/d or the equivalent for more than 3 weeks; methotrexate >12.5 mg/week, cyclosporine, azathioprine, or biological modifiers such as etanercept or infliximab within 3 months of admission; and (5) splenectomy or cirrhosis [11-13]. Patients were excluded if (1) aged < 14 years, (2) experienced pneumonia onset ≥ 48 hours after admission, or (3) positive for human immunodeficiency virus.
The following data were collected on patient and disease characteristics, initial oxygenation strategy, laboratory and microbiological data (blood, nasopharyngeal swabs, sputum, and/or bronchoalveolar lavage samples; bacterial or fungal cultures; viral nucleic acid detection; and antibiotic susceptibility patterns), associated organ dysfunction, and patient outcomes at hospital discharge.
Microbiological samplings were performed, bronchoalveolar lavage (BAL) samples were obtained according to clinical indication or judgement of the attending physician. Sputum, BAL samples or nasopharyngeal swabs were performed for atypical pathogen and viral PCR amplification tests .Respiratory viruses including CMV, RSV, IFV types A and B, PIV, HRV, human metapneumovirus (HMPV), or adenovirus (AdV) and Mycoplasma pneumoniae, Chlamydia pneumoniae, L. pneumophila , Pneumocystisjirovecii (PCP) were detected in nasopharyngeal swab, sputum, endotracheal aspirate (ETA), or BAL fluid using reverse-transcription real time polymerase chain reaction (RT-PCR) (Shanghai Zhijiang Biological Technology, China). Sputum, ETA, BAL samples were evaluated for bacteria cultures and fungal cultures; The Platelia Aspergillus test was used for galactomannan detection (Bio-Rad Laboratories, Marnes-la-Coquette, France).
Pathogen-specific diagnostic criteria
For diagnosing pneumonia caused by Aspergillus, one or more of the following criteria were required: (1) histopathologic or direct microscopic evidence of dichotomous septate hyphae with a positive culture for Aspergillus from tissue, (2) a positive Aspergillus culture from BAL fluid, (3) a galactomannan optical index in BAL fluid ≥ 1, (4) a galactomannan optical index in serum ≥ 0.5; (5) Aspergillus species identified by culture characteristics and microscopically [16,17].
The diagnosis of Pneumocystisjirovecii pneumonia (PCP) required one of the following: (1) high-resolution computed tomography imaging showing diffuse ground glass opacity with patchy distribution; (2) mycological criteria: microscopic examination of the respiratory sample revealing the presence of Pneumocystis cystic or trophic forms; or (3) a positive PCR test for Pneumocystis DNA .
Coinfection was considered if bacteria or fungi were isolated from lower respiratory tract specimens (qualiﬁed sputum, endotracheal aspirate, and BAL) and/or it was indicated by blood samples within 48 h of hospitalization. Nosocomial infection was diagnosed when patients showed clinical signs or symptoms of pneumonia or bacteremia and had a positive culture of a new pathogen obtained from lower respiratory tract specimens and/or blood samples taken ≥ 48 h after admission.
The demographics, clinical characteristics, and pathogen testing results were expressed as mean (± standard deviation), median (interquartile range), or numbers (percentage). Group comparisons were conducted using the Student’s t-test or Wilcoxon rank-sum test for continuous variables with and without normal distributions, respectively. Categorical variables of the two groups were compared using the c2 test.
Statistical analyses were performed using SPSS version 19.0 (SPSS, Inc., Chicago, Illinois). All tests were two-sided, and P-values < 0.05 were considered statistically significant.
Patient and public involvement
No patient or the public were involved in the development of the research question, study design, recruitment, and the conduct of the study.